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Optical microcavity enables single-molecule detection

20 Jul 2007

A nanoscale optical device that can detect individual molecules in a solution could aid the search for cancer therapies.

The nanoscale device, developed by scientists at the California Institute of Technology, works by trapping light around a specially designed microstructure and then observing the changes in optical properties caused by the interaction between this light and different molecules in the solution. According to the researchers, the device could for the first time allow scientists to monitor in real-time how single molecules interact with each other.

The design consists of a regular array of microstructures fabricated on a flat silicon wafer. Each of these structures is called a toroid resonator and consists of a glass ring (about 80 µm wide) resting on a cylindrical silicon stem, which gives it a mushroom-like appearance.

“When light of a particular (resonance) wavelength is coupled into these structures using a waveguide, the optical resonance effects leads to some photons being ‘trapped’ in the periphery of the toroid,” said Caltech’s Andrea Armani. From the top, the light appears to go round in circles inside the toroid – which gives it the appearance of a circular “photon superhighway”.

Whenever a molecule lands in this path, it is bombarded with hundreds of thousands of photons. These collisions release heat, albeit in tiny amounts, which in turn cause the refractive index of the glass to change.

“When this happens, the resonance wavelength also shifts, but by less than 1 nm,” Armani added. “We used a tunable laser and an oscilloscope combined with a highly sensitive detector to ensure that this change in resonance wavelength was accurately determined.”

One of the biggest challenges for the Caltech team has been the development of a microstructure with a very high Quality factor. The Q-factor is a direct indicator of the time for which the photons are trapped – the larger the Q-factor, the longer the lifetime of the photons.

“About 4 years ago, we designed our ultrahigh Q-factor microtoroid structure, and demonstrated Q-factors of 500 million in air. But this was not good enough, as our goal was to specifically identify (not just detect) molecules in the vicinity of the toroid,” explained Armani. The device must also be able to sustain the same properties when placed in water, since most biological specimens are kept in an aqueous medium.

To address these issues, the researchers coated the surface of the toroid with a specific antibody that binds only to one particular molecule. The final device is therefore a resonator array that comprises nine toroids coated with different antibodies.

To test the scheme, the researchers immersed the array in aqueous chamber and then directed trace amounts of the protein interleukin-2 (IL-2) over it using a syringe pump. The results, which have been reported in a recent issue of Science, show that the device can detect and identify tiny concentrations of the protein in the liquid.

According to Armani, the device could for the first time enable real-time monitoring of biological processes such as intra-cellular reactions and cell signalling. Most experiments on single molecules currently rely on attaching labels such as fluorescent dyes to individual molecules. This approach is ideal for tracking pre-existing molecules, but is no good for monitoring experiments.

“A whole range of processes haven’t been studied because of the limitations of label-based detection. This optical resonance detector could allow scientists to observe such events in real-time.” says Armani. Being able to study such real-time experiments is crucially important in many areas, including cancer research, as they allow scientists to see how cells communicate and interact with each other.

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